The proposed South African MRC HPTU would comprise a transdisciplinary team with research capabilities in microbicides, perinatal HIV transmission, and STD control, and expertise in immunology, infectious diseases, epidemiology, biostatistics, behavioral science, clinical trial management, and community mobilization. Ongoing microbicide research within the team includes a Phase I trial of PRO2000/5, a Phase II trial of PC-515, and a Phase III trial of COL-1492. Perinatal HIV research within this group focuses on breastfeeding transmission, and new interventions are being assessed including the extended use of nevirapine as prophylaxis during breastfeeding. Improving STD care to reduce HIV transmission is being tested in a community-based ecological-level trial in Hlabisa, with preliminary data suggesting a beneficial effect. Researchers in this HPTU have extensive experience in the conduct of trials, especially HIV prevention trials (with one-year follow-up rates averaging 85-95 percent). The applicant proposes a range of new and existing cohorts including (1) 1,000 young Hlabisa women (HIV incidence rate = 14.8 percent per year) for a Phase IIb/III microbicide trial, (2) 2,000 mother-infant pairs from three hospitals in Durban (HIV prevalence = 32 percent and vertical transmission rate = 28 percent in 1998), (3) 120 low-risk women from RK Khan hospital for Phase I microbicide trials, (4) 12 communities for a STD intervention trial, and (5) a cohort of 100 discordant couples and 400 sex workers (HIV incidence rate = 18.2 percent per year) for a post-exposure prophylaxis trial. Since this site leads protocols for two HIVNET-funded Phase I trials (PRO2000/5 microbicide and nevirapine during breastfeeding), it could expand to Phase IIb or Phase III trials to assess the efficacy of these interventions. Phase I and Phase II capabilities are well developed in the South African MRC HPTU, and the unit also plans to conduct Phase III trials in large, very high-risk cohorts. Plans include recruitment and follow-up, and in some instances will use global positioning technology to assist in locating subjects. Community preparations for HIV vaccine trials are at an advanced stage; Community Advisory Boards have been established and community education plans are already being implemented. In addition to new ideas on HIV prevention interventions and well-developed clinical trial capability, the South African MRC HPTU also plans to contribute to behavioral, ethical, and community preparation aspects of HIV prevention research.